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Intramolecular Povarov Reactions for the Synthesis of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding to ?-Synuclein and Amyloid-? Fibrils.

ABSTRACT: A BF3·OEt2 catalyzed intramolecular Povarov reaction was used to synthesize 15 chromenopyridine fused thiazolino-2-pyridone peptidomimetics. The reaction works with several O-alkylated salicylaldehydes and amino functionalized thiazolino-2-pyridones, to generate polyheterocycles with diverse substitution. The synthesized compounds were screened for their ability to bind ?-synuclein and amyloid ? fibrils in vitro. Analogues substituted with a nitro group bind to mature amyloid fibrils, and the activity moreover depends on the positioning of this functional group.

SUBMITTER: Adolfsson DE

PROVIDER: S-EPMC7660745 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Intramolecular Povarov Reactions for the Synthesis of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding to α-Synuclein and Amyloid-β Fibrils.

Adolfsson Dan E DE Tyagi Mohit M Singh Pardeep P Deuschmann Adrian A Ådén Jörgen J Gharibyan Anna L AL Jayaweera Sanduni Wasana SW Lindgren Anders E G AEG Olofsson Anders A Almqvist Fredrik F Almqvist Fredrik F

The Journal of organic chemistry 20201025 21

A BF3·OEt2 catalyzed intramolecular Povarov reaction was used to synthesize 15 chromenopyridine fused thiazolino-2-pyridone peptidomimetics. The reaction works with several O-alkylated salicylaldehydes and amino functionalized thiazolino-2-pyridones, to generate polyheterocycles with diverse substitution. The synthesized compounds were screened for their ability to bind α-synuclein and amyloid β fibrils in vitro. Analogues substituted with a nitro group bind t ...[more]

PMID: 33099999

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